Insomnia and microbiota: clinical and pathophysiological relationships

Background. The gut microbiota plays an important role in maintaining human health. The brain-gut axis is currently being actively studied. During the research, it was noted that the intestinal microbiota demonstrates circadian rhythms that interact with the circadian rhythms of the host. Chronic insomnia, in turn, can disrupt microbial circadian rhythms, thereby affecting the composition and function of the intestinal microbiota. Jet lag syndrome causes a significant increase in body weight and blood glucose levels due to its effect on the composition of the human intestinal microbiome. With the change of day and night, the number of Paraprevotella, Fusobacteria and Fusobacteriales in the intestinal microflora increases. The vagus nerve, interacting with the intestinal nervous system, releases nicotinic cholinergic signals to activate intestinal glial cells, which can secrete S-nitrosoglutathione to increase the expression of tight junctional proteins. 5-hydroxytryptamine (5-HT) is an inhibitory neurotransmitter that is synthesized and distributed by about 90% in enterochromaffin cells. Sleep disorders occur when the level of 5-HT in the brain decreases. Currently, it has been proven that dysbiosis of the intestinal microbiota is associated with the development of neuropsychiatric diseases and has a significant impact on human metabolic health. The gut microbiota plays an important role in the bidirectional connection between the brain, the immune system, and the gut (the brain-gut-immunity axis). On the one hand, the microbiota stimulates innate immunity by activating lymphoid tissues located in the intestinal system; on the other hand, interactions between bacterial fragments and receptors (such as TLR9 and the inflammasome) on the surface of epithelial and immune cells activate specific systemic and local immune responses.

Results. The review article presents current data on the mechanisms by which the intestinal microbiota can influence the mental state and quality of sleep and the circadian rhythm of the host, and the role of regular stress on the composition of the microbiota is noted. Strategies have been outlined to improve sleep quality based on lifestyle adjustments, individual nutrition, prebiotics and "psychobiotics" to counteract dysbiosis, potentially associated with sleep disorders.

1. Wang Q., Gao T., Zhang W., et al. Causal relationship between the gut microbiota and insomnia: a two-sample Mendelian randomization study. Front Cell Infect Microbiol. 2024; 14: 1279218.

2. Nie L., Xiang Q., Lin Y., et al. Correlation between symptoms and cognitive function changes in patients with primary insomnia and pathways in gut microbiota. Biochem Biophys Rep. 2024; 37: 101629.

3. Barone M., Martucci M., Sciara G., et al. Towards a personalized prediction, prevention and therapy of insomnia: gut microbiota profile can discriminate between paradoxical and objective insomnia in post-menopausal women. EPMA J. 2024; 15 (3): 471-489.

4. Xie F., Feng Z., Xu B. Metabolic Characteristics of Gut Microbiota and Insomnia: Evidence from a Mendelian Randomization Analysis. Nutrients. 2024; 16 (17): 2943.

5. Chen H. W., Zhou R., Cao B. F., еt al. The predictive, preventive, and personalized medicine of insomnia: gut microbiota and inflammation. EPMA J. 2023; 14 (4): 571-583.

6. Li F. J., Zhang R. Y., Li J. Y., еt al. Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing. Front Microbiol. 2024; 15: 1413218.

7. Guo J., Guo J., Rao X., et al. Exploring the pathogenesis of insomnia and acupuncture intervention strategies based on the microbiota-gut-brain axis. Front Microbiol. 2024; 15: 1456848.

8. Bilal M., Nashwan A. J. Challenges in integrating traditional Chinese medicine and gut microbiota research for insomnia treatment. World J Clin Cases. 2024; 12 (29): 6271-6274.

9. Ma X., Li J., Yang Y. Enhanced cerebral blood f low similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles. Neuroimage. 2024; 297: 120762.

10. Fang J., Wang S., Liu L., et al. Gut microbiota: a potential influencer of insomnia occurring after COVID-19 infection. Front Psychiatry. 2024; 15: 1423715.

11. Even C., Magzal F., Shochat T. Microbiota Metabolite Profiles and Dietary Intake in Older Individuals with Insomnia of Short vs. Normal Sleep Duration. Biomolecules. 2024; 14 (4): 419.

12. Cai Y., Gong D., Xiang T. Markers of intestinal barrier damage in patients with chronic insomnia disorder. Front Psychiatry. 2024; 15: 1373462.

13. Tanaka A., Sanada K., Miyaho K., et al. The relationship between sleep, gut microbiota, and metabolome in patients with depression and anxiety: A secondary analysis of the observational study.PLoS One. 2023; 18 (12): e0296047.

14. Parkar S. G., Kalsbeek A., Cheeseman J. F. Potential role for the gut microbiota in modulating host circadian rhythms and metabolic health. Microorganisms. 2019; 7: 41.

15. Gentile C. L., Weir T. L. The gut microbiota at the intersection of diet and human health. Science. 2018; 362: 776-780.

16. Song D., Yang S. C., Zhang X., Wang Y. The relationship between host circadian rhythms and intestinal microbiota: A new cue to improve health by tea polyphenols. Critical Reviews in Food ScienceandNutrition. 2020; 61: 139-148.

17. Cenit M. C., Matzaraki V., Tigchelaar E. F., Zhernakova A. Rapidly expanding knowledge on the role of the gut microbiome in health and disease. Biochimicaet Biophysica Acta – Molecular Basisof Disease. 2014; 1842: 1981-1992.

18. Yano J. M., Yu K., Donaldson G. P., еt al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015; 161: 264-276.

19. Martin C. R., Osadchiy V., Kalani A., Mayer E. A. The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol. 2018; 6: 133-148.

20. Bonaz B., Bazin T., Pellissier S. The vagus nerve at the interface of the microbiota gut-brain axis. Front Neurosci. 2018; 12: 49.

21. Yu Y. B. Enteric glial cells and their role in the intestinal epithelial barrier. WJG. 2014; 20: 11273.

22. Ning L., Shiqiang S., Pengjie W., et al. The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine. Int J Mol Sci. 2021; 22 (15): 7931.

23. Kirsteen N.B., Kaitlin E.C. Central Neurocircuits Regulating Food Intake in Response to Gut Inputs-Preclinical Evidence Nutrients. 2021; 13 (3): 908.

24. Chih M. C., Chien C. W., Chin L. H., et al. Lactobacillus plantarum PS128 Promotes Intestinal Motility, Mucin Production, and Serotonin Signaling in Mice. ProbioticsAntimicrob, Proteins. 2022; 14 (3): 535-545.

25. Liu K. L., Xu S. J., Chen S. W., et al. Correlation Analysis of Characteristics of Intestinal Microbiota and Cytokine Levels in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome. Nat Sci Sleep. 2024; 16: 1533-1544.

26. Patterson E., Tan H. T. T., Groeger D., et al. Bifidobacterium longum 1714 improves sleep quality and aspects of well-being in healthy adults: a randomized, double-blind, placebo-controlled clinical trial. Sci Rep. 2024; 14 (1): 3725.

27. Loh J. S., Mak W. Q., Tan L. K. S., еt al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther. 2024; 16; 9 (1): 37.

28. Jeong A. H., Hwang J., Jo K. Fermented Gamma Aminobutyric Acid Improves Sleep Behaviors in Fruit Flies and Rodent Models. Int J Mol Sci. 2021; 22 (7): 3537.

29. Zou Q., Han S., Liang J. Alleviating effect of vagus nerve cutting in Salmonella-induced gut infections and anxiety-like behavior via enhancing microbiota-derived GABA. Brain Behav Immun. 2024; 119: 607-620.

30. Fang J., Wang S., Liu L. Gut microbiota: a potential influencer of insomnia occurring after COVID-19 infection. Front Psychiatry. 2024; 15: 1423715.

31. Roncoroni J., Tucker C. M., Wippold G. Sleep as a Predictor of Health-Related Quality of Life among Economically Disadvantaged Black Older Adults. Ethn Dis. 2024; 34 (4): 214-220.

32. Singh K. K., Ghosh S., Bhola A. Sleep and Immune System Crosstalk: Implications for Inflammatory Homeostasis and Disease Pathogenesis. Ann Neurosci. 2024; 20: 09727531241275347.

33. Téfit M. A., Budiman T., Dupriest A., Yew J. Y. Environmental microbes promote phenotypic plasticity in reproduction and sleep behaviour. Mol Ecol. 2023; 32 (18): 5186-5200.

34. Chennaoui M., Sauvet F., Drogou C., et al. Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-a) levels in healthy men. Cytokine. 2011; 56: 318-324.

35. Manchanda S., Singh H., Kaur T., et al. Low-grade neuroinflammation due to chronic sleep deprivation results in anxiety and learning and memory impairments. Mol Cell Biochem. 2018; 449 (1-2): 63-72.

36. Dos Santos A., Galiè S. The Microbiota-Gut-Brain Axis in Metabolic Syndrome and Sleep Disorders: A Systematic Review. Nutrients. 2024; 16 (3): 390.

37. Le L., Miyanishi K., Tanaka J., Majewska A. K. Microglial Regulation of Sleep and Wakefulness. Adv Neurobiol. 2024; 37: 243-260.

38. Kamphuis J., Meerlo P., Koolhaas J. M., Lancel M. Poor sleep as a potential causal factor in aggression and violence. Sleep Med. 2012; 13 (4): 327-334.

39. Manske S. Lifestyle Medicine and the Microbiome: Holistic Prevention and Treatment. Integr Med (Encinitas). 2024; 23 (5): 10-14.

40. Jiang Q., Lin L., Xie F. Metagenomic insights into the microbe-mediated B and K2 vitamin biosynthesis in the gastrointestinal microbiome of ruminants. Microbiome. 2022; 10 (1): 109.

41. Seethaler B., Nguyen N. K., Basrai M. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am J Clin Nutr. 2022; 116 (4): 928-942.

42. Peng K., Xia S., Xiao S., Yu Q. Short-chain fatty acids affect the development of inflammatory bowel disease through intestinal barrier, immunology, and microbiota: A promising therapy? J Gastroenterol Hepatol. 2022; 37 (9): 1710-1718.

43. Seong H. J., Baek Y., Lee S., Jin H. J. Gut microbiome and metabolic pathways linked to sleep quality. Front Microbiol. 2024; 15: 1418773.

44. Silva Y. P., Bernardi A., Frozza R. L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020; 11: 25.

45. Wang J., Zhu N., Su X., et al. Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis. Cells. 2023; 12 (5): 793.

46. Forte N., Marfella B., Nicois A., et al. The short-chain fatty acid acetate modulates orexin/hypocretin neurons: A novel mechanism in gut-brain axis regulation of energy homeostasis and feeding. BiochemPharmacol. 2024; 226: 116383.

47. Aquino G., Benz F., Dressle R. J., еt al. Towards the neurobiology of insomnia: A systematic review of neuroimaging studies. Sleep Med Rev. 2024; 73: 101878.

48. Mueller N. T., Differding M. K., Østbye T., et al. Association of birth mode of delivery with infant faecalmicrobiota, potential pathobionts, and short chain fatty acids: a longitudinal study over the first year of life. BJOG. 2021; 128 (8): 1293-1303.

49. Kortman G. A. M., Hester E. R., Schaafsma Aetal. Gutmicrobiome composition and functionality impact the responsiveness to a dairy-based product containing galacto-oligosaccharides for improving sleep quality in adults. Benef Microbes. 2024; 15 (4): 373-385.

50. Andrew R., Izzo A. A. Highlights into the pharmacology of nutraceuticals. Br J Pharmacol. 2020; 177 (6): 1209-1211.

51. Gao R., Tian S., Wang J., Zhu W. Galacto-oligosaccharides improve barrier function and relieve colonic inflammation via modulating mucosa-associated microbiota composition in lipopolysaccharides-challenged piglets. J Anim Sci Biotechnol. 2021; 12 (1): 92.

52. Yao C., Jiang N., Sun X., et al. Effects of inulin-type oligosaccharides (JSO) from Cichoriumintybus L. on behavioral deficits induced by chronic restraint stress in mice and associated molecular alterations. Front Pharmacol. 2024; 15: 1484337.

53. Sun Q., Yin S., He Y., et al. Biomaterials and Encapsulation Techniques for Probiotics: Current Status and Future Prospects in Biomedical Applications. Nanomaterials (Basel). 2023; 13 (15): 2185.

54. Cheraghpour M., Fatemi N., Shadnoush M., et al. Immunomodulation aspects of gut microbiome-related interventional strategies in colorectal cancer. Med Oncol. 2024; 41 (9): 231.

55. Santi D., Debbi V., Costantino F., et al. Microbiota composition and probiotics supplementations on sleep quality – A systematic review and meta-analysis. Clocks Sleep. 2023; 5: 770-792.

56. Horvath A., Wagner-Skacel J., Stiegelbauer V., Stadlbauer V. A probiotic to improve sleep quality during COVID-19 pandemic: A questionnaire study. J Biotechnol Bio Med. 2023; 06: 80-91.

57. Fang H., Yao T., Li W., et al. Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study. Front Microbiol. 2023; 14: 1299816.